The histopathology classification of lung cancers and cell lines is based on criteria detectably by light microscopy such as cell size and shape as well as growth patterns. Attempts to characterize the tumors by cell type are generally beyond the resolution of light microscopy. This is the reason by tumors of a given histopathology type may be comprised of a large variety of different cell types and of mixtures of cells. The reactor of cells and tissues including tumors to chemicals and drugs require, therefore, that the tumors be classified by cell type and differentiation using electron microscopy. We therefore investigate surgical samples of lung cancers as well as the cell lines derived from them by electron microscopy and classify them by cell type and differentiation. Since it is presently not known to what extent the HCCL change during prolonged life in vitro, we also monitor the cells lines at early and late passages. To date, we have processed 31 surgical samples which are currently being diagnosed. A total of 25 cell lines has thus far been investigated which resulted in modified or altered diagnosis in many cases. Some of the lines were examined at early and late passages and there is evidence that, in particular, well differentiated tumors tend to change morphologically after several passages in vitro. We are using the ultrastructural classification of tumors and cell lines as a basis for the design of comparative biochemical and pharmacological experiments (within LETM and in collaboration with other institutes) aimed at elucidating cell types specific reactions.